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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

TLR3 Gene

protein-coding GIFtS: 71
GCID: GC04P186990

Toll-Like Receptor 3

Microbiology & Infectious Diseases Congress

94 related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
About This Section

Aliases
Toll-Like Receptor 3¹ ²
CD283²
IIAE2²
CD283 Antigen³

External Ids:	HGNC: 11849¹	Entrez Gene: 7098²	Ensembl: ENSG00000164342⁷	OMIM: 603029⁵	UniProtKB: O15455³

Export aliases for TLR3 gene to outside databases

Previous GC identifers: GC04P188024 GC04P187670 GC04P187574 GC04P187686 GC04P187365 GC04P187227 GC04P182742

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for TLR3 Gene:

The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in

pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share

structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are

expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective

immunity. The various TLRs exhibit different patterns of expression. This receptor is most abundantly expressed in

placenta and pancreas, and is restricted to the dendritic subpopulation of the leukocytes. It recognizes dsRNA

associated with viral infection, and induces the activation of NF-kappaB and the production of type I interferons. It

may thus play a role in host defense against viruses. Use of alternative polyadenylation sites to generate different

length transcripts has been noted for this gene. (provided by RefSeq, Jul 2008)

GeneCards Summary for TLR3 Gene:

TLR3 (toll-like receptor 3) is a protein-coding gene. Diseases associated with TLR3 include herpes simplex, and herpes simplex encephalitis, and among its related super-pathways are Toll-like receptor signaling pathway and Immune response Role of TLRs 3 and 4 in cell antiviral response: TICAM1-specific signaling pathways. GO annotations related to this gene include double-stranded RNA binding and receptor activity. An important paralog of this gene is ENSG00000173366.

UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455

Function: Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response

against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a nucleotide-sensing

TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to

NF-kappa-B activation, cytokine secretion and the inflammatory response

summary for TLR3 Gene:

Toll-like receptors (TLRs) are single transmembrane cell-surface receptors, which have a key role in the

innate immune system. TLRs generally exist as homodimers (although TLR2-TLR6 heterodimers have been

reported) and are found on immune cells such as macrophages, B lymphocytes and mast cells. Toll-like

receptors are activated by molecules associated with biological threat and are highly specific towards

evolutionary conserved entities on microbes, such as bacterial cell-surface lipopolysaccharides, flagella

and unmethylated CpG islands. It has been suggested that some toll-like receptors may have endogenous

ligands, such as Hsp60 and fibrinogen, and this has promoted speculation that endogenous toll-like receptor

activators may have a pathological role in autoimmune disease. Activation of toll-like receptors initiates

downstream signaling cascades, initially via the adapter molecules MyD88, Trap, Trif and Tram, which

converge on the PI 3-K and NF-kappaB pathways and regulate intracellular kinases and gene expression. This

can stimulate an inflammatory and/or antigen-specific immune response. The signaling cascade coupled to

toll-like receptor activation is very similar to that of interleukin-1 receptor (IL-1R) activation.

Gene Wiki entry for TLR3 (TLR 3) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000004.11 NC_018915.2 NT_016354.19

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the TLR3 gene promoter:
AP-1 ATF-2 NF-AT NF-AT2 POU2F1 POU2F1a NF-AT3 STAT3 c-Jun NF-AT1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: TLR3 promoter sequence

Search SABiosciences Chromatin IP Primers for TLR3

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat TLR3

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 4q35 Ensembl cytogenetic band: 4q35.1 HGNC cytogenetic band: 4q35

TLR3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TLR3 gene location

GeneLoc information about chromosome 4 GeneLoc Exon Structure

GeneLoc location for GC04P186990: view genomic region (about GC identifiers)

Start:	186,990,306 bp from pter	End:	187,006,255 bp from pter
Size:	15,950 bases	Orientation:	plus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455 (See protein sequence)

Recommended Name: Toll-like receptor 3 precursor

Size: 904 amino acids; 103829 Da

Subunit: Monomer and homodimer; dimerization is triggered by ligand-binding and is required for TLR3 signaling.

Interacts (via transmembrane domain) with UNC93B1 (By similarity). Interacts with TICAM1 (via the TIR domain);

mediates TLR3 signaling. Interacts with SRC; upon binding of double-stranded RNA

Subcellular location: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endosome membrane

4 PDB 3D structures from and Proteopedia for TLR3:

1ZIW (3D)

2A0Z (3D)

3ULU (3D)

3ULV (3D)

Secondary accessions: Q4VAL2

Explore the universe of human proteins at neXtProt for TLR3: NX_O15455

Explore proteomics data for TLR3 at MOPED

Post-translational modifications:

UniProtKB: Heavily N-glycosylated, except on that part of the surface of the ectodomain that is involved in ligand binding

View modification sites using PhosphoSitePlus

View neXtProt modification sites for NX_O15455

TLR3 Protein expression data from MOPED¹, PaxDb² and MAXQB³ : About this image

REFSEQ proteins: NP_003256.1

ENSEMBL proteins:

ENSP00000296795 ENSP00000423386 ENSP00000423684

Reactome Protein details: O15455
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	Cloud-Clone Corp. Proteins for TLR3

Gene Ontology (GO): 5/10 cellular component terms (GO ID links to tree view) (see all 10): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000139	Golgi membrane	TAS	--
GO:0005737	cytoplasm	IDA	19740627
GO:0005765	lysosomal membrane	IDA	17897319
GO:0005789	endoplasmic reticulum membrane	TAS	--
GO:0005887	integral to plasma membrane	TAS	9435236

TLR3 for ontologies About GeneDecksing

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	Cloud-Clone Corp. ELISAs for TLR3 Cloud-Clone Corp. CLIAs for TLR3

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

HGNC Gene Families:

CD: CD molecules

IUPHAR Guide to PHARMACOLOGY protein family classification: TLR3

Toll-like receptor family

5/6 InterPro protein domains (see all 6):

IPR000483 Cys-rich_flank_reg_C

IPR000372 LRR-contain_N

IPR001611 Leu-rich_rpt

IPR000157 TIR_dom

IPR027173 TLR3

Graphical View of Domain Structure for InterPro Entry O15455

ProtoNet protein and cluster: O15455

4 Blocks protein domains:

IPB000157 TIR domain

IPB000372 Cysteine-rich flanking region

IPB000483 Cysteine-rich flanking region

IPB001611 Leucine-rich repeat signature

UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455

Domain: ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18 (By similarity)

Similarity: Belongs to the Toll-like receptor family

Similarity: Contains 22 LRR (leucine-rich) repeats

Similarity: Contains 1 LRRCT domain

Similarity: Contains 1 LRRNT domain

Similarity: Contains 1 TIR domain

TLR3 for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: TLR3_HUMAN, O15455

Function: Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response

against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a nucleotide-sensing

TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to

NF-kappa-B activation, cytokine secretion and the inflammatory response

Genatlas biochemistry entry for TLR3:

Drosophila transmembrane receptor Toll homolog 3,with the major transcripts,predominantly expressed in placenta and

pancreas,involved in immune defense

Gene Ontology (GO): 4 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003725	double-stranded RNA binding	NAS	12054664
GO:0004872	receptor activity	TAS	10426995
GO:0004888	transmembrane signaling receptor activity	NAS	12054664
GO:0005515	protein binding	IPI	16858407

TLR3 for ontologies About GeneDecksing

Phenotypes:
11 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for Tlr3):

behavior/neurological	cardiovascular system	endocrine/exocrine gland	homeostasis/metabolism	immune system
mortality/aging	muscle	nervous system	reproductive system	respiratory system
tumorigenesis

TLR3 for phenotypes About GeneDecksing

Animal Models:
Mouse knock-outs for TLR3: Tlr3^tm1Flv Tlr3^tm1Ttg

inGenious Targeting Laboratory - Custom generated mouse model solutions for TLR3

inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for TLR3

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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TLR3

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene).
About This Section

SuperPaths for TLR3 About (see all 21)

See pathways by source

SuperPath

Contained pathways About

Toll-like receptor signaling pathway

	Toll-like receptor signaling pathway	0.93			Hepatitis B	0.31
	Toll-like receptor signaling pathway	0.93

Immune response TLR3 and TLR4 induce TICAM1-specific signaling pathway

Immune response TLR3 and TLR4 induce TICAM1-specific signaling pathway

0.91

Immune response Role of TLRs 3 and 4 in cell antiviral response: TICAM1-specific signaling pathways

0.91

TRAF6 Mediated Induction of proinflammatory cytokines

Activated TLR4 signalling	0.87	Toll Like Receptor 4 (TLR4) Cascade	0.87
MyD88-independent cascade	0.87	Toll-Like Receptors Cascades	0.87
Toll Like Receptor 3 (TLR3) Cascade	0.87	TRIF-mediated TLR3/TLR4 signaling	0.86

TRAF6 mediated induction of TAK1 complex

	TRAF6 mediated induction of TAK1 complex	0.56			IKK complex recruitment mediated by RIP1	0.42
	Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon	0.50			TRIF-mediated programmed cell death	0.32

Toll-Like receptor Signaling Pathways

	Toll-Like receptor Signaling Pathways	0.59			Inflammasome Activation Pathways	0.52
	NOD-like Receptor Signaling Pathways	0.59

Pathways by source See SuperPaths
Show all pathways

1 EMD Millipore Pathway for TLR3

Immune response Role of TLRs 3 and 4 in cell antiviral response- TICAM1-specific signaling pathways

5/6 R&D Systems Pathways for TLR3 (see all 6)

	NOD-like Receptor Signaling Pathways
	Inflammasome Activation Pathways
	IL-21 Signaling and its Primary Biological Effects in Different Immune Cell Types
	Th1 Differentiation
	Toll-Like receptor Signaling Pathways

5/9 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for TLR3 (see all 9)

	NF-KappaB (p50-p65) Pathway
	Toll-Like Receptors Pathway
	TRAF Pathway
	TREM1 Pathway
	Colorectal Cancer Metastasis

1 Cell Signaling Technology (CST) Pathway for TLR3

NF-kappaB Signaling

1 Tocris Bioscience Pathway for TLR3

Toll-like Receptor Pathway

1 GeneGo (Thomson Reuters) Pathway for TLR3

Immune response TLR3 and TLR4 induce TICAM1-specific signaling pathway

1 BioSystems Pathway for TLR3

Toll-like receptor signaling pathway

1 Sino Biological Pathway for TLR3

NF-kB (NFkB) Pathway

5/13 Reactome Pathways for TLR3 (see all 13)

	IKK complex recruitment mediated by RIP1
	Toll Like Receptor 4 (TLR4) Cascade
	Toll-Like Receptors Cascades
	TRIF-mediated programmed cell death
	Toll Like Receptor 3 (TLR3) Cascade

5 Kegg Pathways (Kegg details for TLR3):

	Toll-like receptor signaling pathway
	Hepatitis C
	Hepatitis B
	Influenza A
	Herpes simplex infection

TLR3 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for TLR3

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/66 Interacting proteins for TLR3 (O15455^{2, 3} ENSP00000296795⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 66)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
PIK3R1	P27986²^,³, ENSP00000274335⁴	MINT-2840093 MINT-2840114 I2D: score=2 STRING: ENSP00000274335
ENSG00000184494	Q99519³	I2D: score=1
ENSG00000223957	Q99519³	I2D: score=1
ENSG00000227129	Q99519³	I2D: score=1
ENSG00000227315	Q99519³	I2D: score=1

About this table

Gene Ontology (GO): 5/39 biological process terms (GO ID links to tree view) (see all 39): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0002224	toll-like receptor signaling pathway	TAS	--
GO:0002756	MyD88-independent toll-like receptor signaling pathway	TAS	--
GO:0006952	defense response	--	--
GO:0006954	inflammatory response	IEA	--
GO:0006972	hyperosmotic response	NAS	12054664

TLR3 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, IUPHAR, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

TLR3 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Enzo Life Sciences drugs & compounds for TLR3

Compounds for TLR3 available from Tocris Bioscience About this table

Compound	Action	CAS #
Pam2CSK4	TLR2/6 agonist; induces TNF-alpha production	[868247-72-7]
Resiquimod	Toll-like receptor 7 (TLR7) agonist	[144875-48-9]
Pam3CSK4	TLR1/2 agonist; induces cytokine production	[112208-00-1]
Poly(I:C)	TLR3 agonist	[42424-50-0]
Imiquimod	Toll-like receptor 7 (TLR7) agonist	[99011-02-6]

1 IUPHAR Ligand for TLR3 (TLR3) About this table

Ligand	Type	Action	Affinity	Pubmed IDs
polyIC	Agonist	Agonist		11607032

10/22 Novoseek inferred chemical compound relationships for TLR3 gene (see all 22) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
poly(i-c)	92.4	66	16384532 (3), 15845391 (3), 16142732 (3), 14688319 (2) (see all 38)
polyinosinic-polycytidylic acid	92.1	72	17962643 (4), 19452017 (4), 19154402 (2), 18949355 (2) (see all 36)
flagellin	77	14	16365459 (1), 19294011 (1), 19955831 (1), 19740321 (1) (see all 14)
inosine monophosphate	74.2	13	17182588 (3), 17573354 (1), 18715647 (1), 15196204 (1) (see all 11)
peptidoglycan	68.8	16	16365459 (1), 17114468 (1), 16670332 (1), 14996826 (1) (see all 12)
rantes	67.9	14	19121387 (3), 19452017 (2), 16436653 (1), 14517278 (1) (see all 9)
lipoteichoic acid	58.1	4	17114468 (1), 15652398 (1), 16052591 (1), 16175622 (1)
tab-2	52.8	3	14982987 (2), 12609980 (1)
2',5'-oligoadenylate	52.8	2	17669408 (1)
imiquimod	51.6	2	19578865 (1), 19643938 (1)

1 PharmGKB related drug/compound annotation for TLR3 gene About this table

Drug/compound	PharmGKB Annotation
Measles vaccines	CA

Search CenterWatch for drugs/clinical trials and news about TLR3

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for TLR3 gene:

NM_003265.2

Unigene Cluster for TLR3:

Toll-like receptor 3

Hs.657724 [show with all ESTs]

Unigene Representative Sequence: BC068487

5 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000296795(uc003iyq.3) ENST00000513189 ENST00000512264(uc011ckz.2 uc003iyr.3)

ENST00000504367 ENST00000508051

Congresses - knowledge worth sharing:
European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat TLR3
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat TLR3

Additional mRNA sequence:

AB445631.1 AK302143.1 AK314208.1 BC017954.1 BC043204.2 BC059372.1 BC068487.1 BC094737.1

BC096333.1 BC096334.3 BC096335.1 DQ445682.1 DQ470075.1 DQ470076.1 DQ470077.1 DQ470078.1

DQ470079.1 U88879.1

4 DOTS entries:

DT.109361 DT.100664575 DT.101977909 DT.99984982

24/50 AceView cDNA sequences (see all 50):

AU135937 BC068487 NM_003265 CF528559 BQ007482 CF529473 BX104394 BU624267

BX489646 CF994731 CB988158 BC043204 BU950410 CF994235 BX489678 BU853465

BF971051 BU929797 CB960574 CD109430 BC059372 BG573455 BF594247 CB989983

GeneLoc Exon Structure

3 Alternative Splicing Database (ASD) splice patterns (SP) for TLR3 About this scheme

ExUns:	1	^	2	^	3	^	4a	·	4b	^	5a	·	5b	·	5c	^	6
SP1:							-		-
SP2:									-
SP3:

ECgene alternative splicing isoforms for TLR3

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

TLR3 expression in normal human tissues (normalized intensities) TLR3 embryonic expression: see
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: CACTCTGTTT

About this image

TLR3 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database

5/2 selected tissues (see all 2) fully expand


Skeletal Muscle (Muscoskeletal System) fully expand to see all 2 entries
Mononuclear Myocytes Hyoid Arch Muscles

Placenta (Extraembryonic Tissues)

-- (Gastrointestinal Tract)
colon

See TLR3 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for TLR3

SOURCE GeneReport for Unigene cluster: Hs.657724

UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455

Tissue specificity: Expressed at high level in placenta and pancreas. Also detected in CD11c+ immature dendritic cells.

Only expressed in dendritic cells and not in other leukocytes, including monocyte precursors. TLR3 is the TLR that is

expressed most strongly in the brain, especially in astrocytes, glia, and neurons

SABiosciences Expression via Pathway-Focused PCR Arrays including TLR3 (see all 8):

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Toll-Like Receptor Signaling Pathway in human mouse rat

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Inflammatory Response & Autoimmunity 384HT in human mouse rat

Innate & Adaptive Immune Responses in human mouse rat

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of chordates.

Orthologs for TLR3 gene from 4/12 species (see all 12) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Tlr3^{1 , 5}	toll-like receptor 3^{1, 5}	81.31(n)¹ 79.93(a)¹		8 (25.31 cM)⁵ 142980¹ NM_126166.4¹ NP_569054.2¹ 45395665⁵
chicken (Gallus gallus)	Aves	TLR3¹	toll-like receptor 3	67.01(n) 62.06(a)		422720 NM_001011691.3 NP_001011691.3
lizard (Anolis carolinensis)	Reptilia	TLR3⁶ --	Uncharacterized protein	58(a) 24(a)	1 ↔ 1 possible ortholog	5(112305568-112319535) 2(122504100-122506901)
zebrafish (Danio rerio)	Actinopterygii	tlr3¹	toll-like receptor 3	52.99(n) 49.2(a)		403126 NM_001013269.2 NP_001013287.2

ENSEMBL Gene Tree for TLR3 (if available)
TreeFam Gene Tree for TLR3 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for TLR3 gene

ENSG00000173366² CD180² TLR7² TLR1² TLR9² TLR5² TLR10² TLR4²

TLR8² TLR6² TLR2²

2 SIMAP similar genes for TLR3 using alignment to 7 protein entries: TLR3_HUMAN (see all proteins):

TLR2 TLR10

TLR3 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455

Polymorphism: The Phe-412 allele (dbSNP:rs3775291) occurs with a frequency of 30% in populations with European and

Asian ancestry, and confers some natural resistance to HIV-1 infection

SNP ID	Valid	Clinical significance	Chr 4 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
VAR_054887⁴		Herpes simplex encephalitis 2 (HSE2)⁴	--	see VAR_054887	2	P S	mis⁴		0	--	--	--	--
rs121434431^1,2	C,F	other¹	186763303(+)	`GTGGTC/TCCATT`	2	P S	mis¹		1		NA	4550
rs36027624^1,2	C	--	182754573(+)	`AAAAA-/A/AA AAAAA`	1	--	int¹		2		NA CSA	4
rs115313599^1,2	C,F	--	186747149(+)	`GGACTC/GAAGTG`	1	--	us2k¹		1		WA	118
rs139507674^1,2		--	186747253(+)	`ACCACA/GTTGCC`	1	--	us2k¹		0	--	--	--	--
rs145586023^1,2		--	186747290(+)	`AAGCAA/GTCTCC`	1	--	us2k¹		0	--	--	--	--
rs75217467^1,2	C,F	--	186747300(+)	`CTAAAG/ATGTTG`	1	--	us2k¹		2		CSA WA	120
rs182928749^1,2		--	186747430(+)	`AATGTA/GCAGTA`	1	--	us2k¹		0	--	--	--	--
rs147725378^1,2		--	186747470(+)	`AACTAA/GCAAGA`	1	--	us2k¹		0	--	--	--	--
rs187045018^1,2		--	186747588(+)	`AAGTCA/GTGGGA`	1	--	us2k¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for TLR3 (186990306 - 187006255 bp)

Structural Variations
Database of Genomic Variants (DGV) 6 variations for TLR3: About this table

Variant ID	Type	Subtype	PubMed ID
esv2677545	CNV	Deletion	23128226
dgv683n27	CNV	Gain	19166990
nsv470097	CNV	Gain	18288195
dgv5852n71	CNV	Gain	21882294
nsv881424	CNV	Gain	21882294
dgv5851n71	CNV	Gain	21882294

Human Gene Mutation Database (HGMD): TLR3

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

TLR3 for disorders           About GeneDecksing

OMIM gene information: 603029
OMIM disorders: 613002
UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455

Herpes simplex encephalitis 2 (HSE2) [MIM:613002]: A rare complication of human herpesvirus 1 (HHV-1)

infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic

necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache,

seizures, stupor, and often coma, frequently with a fatal outcome. Note=Disease susceptibility is associated with

variations affecting the gene represented in this entry. TLR3 mutations predispose otherwise healthy individuals to

isolated herpes simplex encephalitis through a mechanism that involves impaired IFNs production and reduced immune

defense against viral infection in the central nervous system

20/94 diseases for TLR3 (see all 94): About MalaCards

herpes simplex herpes simplex encephalitis encephalitis measles

west nile virus allergic conjunctivitis septic arthritis molluscum contagiosum

subacute sclerosing panencephalitis protein c deficiency stevens-johnson syndrome hyper ige syndrome

tick-borne encephalitis influenza bronchiolitis bronchiolitis obliterans

pandas biliary atresia rubella hepatitis a

5 diseases from the University of Copenhagen DISEASES database for TLR3:

Encephalitis Melanoma Influenza Herpes simplex

Asthma

Congresses - knowledge worth sharing:
The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014
Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

10/29 Novoseek inferred disease relationships for TLR3 gene (see all 29) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
virus infection	73.1	57	16877304 (2), 14575692 (2), 19452017 (2), 12672806 (2) (see all 36)
inflammation	48.6	13	19752565 (2), 20387535 (2), 18403353 (1), 20483774 (1) (see all 9)
hepatitis c chronic	38.3	1	19475618 (1)
necrosis	32.7	9	14729660 (1), 15579900 (1), 16510559 (1), 18765427 (1) (see all 9)
melanoma	32.1	27	17671143 (4), 19001446 (3), 19470740 (2), 17142768 (1) (see all 14)
hepatitis c	30.8	3	19625408 (2), 18021446 (1)
influenza	30.4	10	15579900 (3), 19231996 (3), 16399790 (2), 16517210 (1) (see all 5)
bacterial infections	27.2	1	18083507 (1)
herpes simplex	23.9	3	19025601 (1), 16847112 (1)
pouchitis	20.9	3	16770571 (2)

Genetic Association Database (GAD): TLR3
Human Genome Epidemiology (HuGE) Navigator: TLR3 (55 documents)

Export disorders for TLR3 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for TLR3 gene, integrated from 9 sources (see all 665):
(articles sorted by number of sources associating them with TLR3)

Utopia: connect your pdf to the dynamic
world of online information

Toll-like receptor 3 and geographic atrophy in age-related macular degeneration. (PubMed id 18753640)^{1, 2, 4, 9} Yang Z.... Zhang K. (2008)
A family of human receptors structurally related to Drosophila Toll. (PubMed id 9435236)^{1, 2, 3} Rock F.L.... Bazan J.F. (1998)
TLR3 gene polymorphisms and liver disease manifestati ons in chronic hepatitis C. (PubMed id 19475618)^{1, 4, 9} Askar E....Mihm S. (2009)
Investigation of the [-/A]8 and C1236T genetic variat ions within the human Toll-like receptor 3 gene for association with multiple s clerosis. (PubMed id 20483009)^{1, 4, 9} Szvetko A.L....Griffiths L.R. (2010)
Crystal structure of human toll-like receptor 3 (TLR3) ectodomain. (PubMed id 15961631)^{1, 2, 9} Choe J....Wilson I.A. (2005)
Single-nucleotide polymorphisms in genes encoding tol l-like receptor -2, -3, -4, and -9 in case-control study with breast cancer. (PubMed id 19810822)^{1, 4, 9} Etokebe G.E....DembiA8 Z. (2009)
Toll-like receptor polymorphisms and age-related macular degeneration. (PubMed id 18385087)^{1, 4, 9} Edwards A.O....Tosakulwong N. (2008)
Polymorphisms in toll-like receptor 4 and toll-like r eceptor 9 influence viral load in a seroincident cohort of HIV-1-infected indiv iduals. (PubMed id 19855253)^{1, 4, 9} Pine S.O....Bochud P.Y. (2009)
Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. (PubMed id 18946062)^{1, 4, 9} Bochud P.Y....Boeckh M. (2008)
Innate immunity of the ocular surface and ocular surface inflammatory disorders. (PubMed id 18813073)^{1, 4, 9} Ueta M. (2008)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 7098	HGNC: 11849	AceView: TLR3	Ensembl:ENSG00000164342	euGenes: HUgn7098
ECgene: TLR3	Kegg: 7098	H-InvDB: TLR3

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for TLR3	Pharmacogenomics, SNPs, Pathways
TLR3base	http://bioinf.uta.fi/TLR3base/

Intellectual Property for TLR3 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for TLR3 gene:
Search GeneIP for patents involving TLR3

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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